Research Papers:

Targeting the facilitative glucose transporter GLUT1 inhibits the self-renewal and tumor-initiating capacity of cancer stem cells

Keita Shibuya, Masashi Okada, Shuhei Suzuki, Manabu Seino, Shizuka Seino, Hiroyuki Takeda and Chifumi Kitanaka _

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Oncotarget. 2015; 6:651-661. https://doi.org/10.18632/oncotarget.2892

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Keita Shibuya1,2,3,*, Masashi Okada1,*, Shuhei Suzuki1,4, Manabu Seino1,5, Shizuka Seino1,2,3,6, Hiroyuki Takeda1,4 and Chifumi Kitanaka1,2,3,6

1 Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan

2 Oncology Research Center, Research Institute for Advanced Molecular Epidemiology, Yamagata University, Yamagata, Japan

3 Global COE program for Medical Sciences, Japan Society for Promotion of Science, Tokyo, Japan

4 Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan

5 Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan

6 Research Institute for Promotion of Medical Sciences, Yamagata University School of Medicine, Yamagata, Japan

* These authors contributed equally to this work


Chifumi Kitanaka, email:

Keywords: cancer initiating cell, glioma, tumorigenicity, xenograft analysis

Received: August 11, 2014 Accepted: November 25, 2014 Published: November 26, 2014


Increased glucose metabolism is now recognized as an emerging hallmark of cancer. Recent studies have shown that glucose metabolism is even more active in cancer stem cells (CSCs), a rare population of cancer cells with the capacity to self-renew and initiate tumors, and that CSCs are dependent on glycolysis for their survival/growth. However, the role of glucose metabolism in the control of their self-renewal and tumor-initiating capacity per se still remains obscure. Moreover, much remains unknown as to which of the numerous molecules involved in the glucose metabolism is suitable as a target to control CSCs. Here we demonstrate that the facilitative glucose transporter GLUT1 is essential for the maintenance of pancreatic, ovarian, and glioblastoma CSCs. Notably, we found that WZB117, a specific GLUT1 inhibitor, could inhibit the self-renewal and tumor-initiating capacity of the CSCs without compromising their proliferative potential in vitro. In vivo, systemic WZB117 administration inhibited tumor initiation after implantation of CSCs without causing significant adverse events in host animals. Our findings indicate GLUT1-dependent glucose metabolism has a pivotal role not only in the growth and survival of CSCs but also in the maintenance of their stemness and suggest GLUT1 as a promising target for CSC-directed cancer therapy.

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